cannabidiol and Substance-Related-Disorders

Substance-use disorders are pervasive, comorbid with a plethora of disease and possess limited treatment options. Medicinal cannabinoids have been proposed as a novel potential treatment based on preclinical/animal trials. The objective of this study was to examine the efficacy and safety of potential therapeutics targeting the endocannabinoid system in the treatment of substance-use disorders. We performed a scoping review using a systematic approach of systematic reviews, narrative reviews, and randomised control trials that utilised cannabinoids as treatment for substance-use disorders. For this scoping review we used the PRISMA guidelines, a framework for systematic reviews and meta-analyses, to inform our methodology. We conducted a manual search of Medline, Embase, and Scopus databases in July 2022. Of the 253 results returned by the databases, 25 studies including reviews were identified as relevant, from which 29 randomised controlled trials were derived and analysed via a primary study decomposition. This review captured a small volume of highly heterogenous primary literature investing the therapeutic effect of cannabinoids for substance-use disorders. The most promising findings appeared to be for cannabis-use disorder. Cannabidiol appeared to be the cannabinoid showing the most promise for the treatment of multiple-substance-use disorders.

Topics: Animals; Cannabidiol; Cannabinoids; Cannabis; Humans; Randomized Controlled Trials as Topic; Substance-Related Disorders

The drug poisoning crisis throughout North America necessitates novel harm reduction approaches. Emerging evidence suggests that cannabidiol (CBD) may have some utility as a harm reduction modality for those with problematic substance use. This rapid review aimed to synthesize available evidence on CBD as a potential harm reduction tool for people who use drugs while providing clinical and research insights.. A systematic search in EMBASE, MEDLINE, CENTRAL, and CINAHL was completed in July 2022. For inclusion, studies had to meet the following criteria: (1) drawn from an adult population of people who use drugs; (2) investigates CBD as an intervention for problematic substance use or harm reduction-related outcomes; (3) be published after the year 2000 and in English; and (4) be primary research or a review article. A narrative synthesis was used to group outcomes relevant to harm reduction and provide clinical and research insights.. We screened 3,134 records, of which 27 studies (5 randomized trials) were included. The evidence remains limited, but available studies support the potential utility of CBD to reduce drug-induced craving and anxiety in opioid use disorder. There were low-quality studies suggesting that CBD may improve mood and general well-being of people who use drugs. Evidence suggests that CBD monotherapy may not be an adequate harm reduction strategy for problematic substance use but rather an adjunct to the standard of care.. Low-quality evidence suggests that CBD may reduce drug cravings and other addiction-related symptoms and that CBD may have utility as an adjunct harm reduction strategy for people who use drugs. However, there is a significant need for more research that accurately reflects CBD dosing and administration regimens used in a real-world context.

Topics: Adult; Anxiety; Cannabidiol; Harm Reduction; Humans; Pharmaceutical Preparations; Substance-Related Disorders

Cannabidiol (CBD) is one of the major constituents of Cannabis sativa L. that lacks psychotomimetic and rewarding properties and inhibits the rewarding and reinforcing effects of addictive drugs such as cocaine, methamphetamine (METH), and morphine. Additionally, CBD's safety profile and therapeutic potential are currently evaluated in several medical conditions, including pain, depression, movement disorders, epilepsy, multiple sclerosis, Alzheimer's disease, ischemia, and substance use disorder. There is no effective treatment for substance use disorders such as addiction, and this review aims to describe preclinical and clinical investigations into the effects of CBD in various models of opioid, psychostimulant, cannabis, alcohol, and nicotine abuse. Furthermore, the possible mechanisms underlying the therapeutic potential of CBD on drug abuse disorders are reviewed.. The current review considers and summarizes the preclinical and clinical investigations into CBD's effects in various models of drug abuse include opioids, psychostimulants, cannabis, alcohol, and nicotine.. Several preclinical and clinical studies have proposed that CBD may be a reliable agent to inhibit the reinforcing and rewarding impact of drugs.. While the currently available evidence converges to suggest that CBD could effectively reduce the rewarding and reinforcing effects of addictive drugs, more preclinical and clinical studies are needed before CBD can be added to the therapeutic arsenal for treating addiction.

Topics: Animals; Cannabidiol; Cannabinoid Receptor Modulators; Humans; Substance-Related Disorders

Cannabidiol (CBD) is a phytocannabinoid found in the Cannabis plant. CBD has received significant medical attention in relation to its anticonvulsant, anxiolytic, and antipsychotic characteristics. An increasing number of studies focusing on the anti-addictive properties of CBD have recently been published. In this systematic review, we aim to offer a comprehensive overview of animal and human studies regarding the impact of CBD on substance use disorders (SUDs).. A systematic search was performed on the PubMed database in February 2021. We included all articles assessing the effects of CBD on substance use disorders.. The current systematic review suggests that CBD might offer promising therapeutic potential for the treatment of SUD, based on available animal and human studies. Animal studies showed a positive impact of CBD in the context of alcohol, opioids, and methamphetamine use (e.g., diminishing of drug-seeking behaviors). The results for cocaine use were mixed among reviewed studies, and CBD was not found to have an effect in animal studies on cannabis use. No animal study was identified that focused on the impact of CBD on nicotine use. Human studies showed a positive impact of CBD in the context of nicotine, cannabis, and opioid use (e.g., frequency and quantity of consumption). In contrast, CBD was not found to have an effect in human studies on cocaine or alcohol use. No human study was identified that investigated the impact of CBD on methamphetamine use.. CBD might offer promising therapeutic potential for the treatment of SUD, especially for nicotine, cannabis, and opioid use disorders, based on available human studies. The available research evidence is, however, sparse and more research on humans is needed.

Topics: Animals; Cannabidiol; Cannabis; Cocaine; Humans; Methamphetamine; Nicotine; Substance-Related Disorders

Cannabidiol (CBD) products lacking regulatory approval are being used to self-treat a myriad of conditions and for their unsubstantiated health benefits. The scientific evidence supporting these claims largely arises not from controlled clinical trials, but from the recognition that CBD has numerous biological targets. Yet, CBD is commonly consumed and often in over-the-counter products that are unapproved and of unknown composition. Epidiolex® is the only product that has undergone rigorous pharmacokinetic assessment and testing in clinical trials; it was approved as a non-scheduled drug by the U.S. Food and Drug Administration for the treatment of intractable childhood-onset seizures. However, studies investigating CBD for other medical conditions are limited in number and often lack the scientific rigor, controls, or sample sizes required to draw clinically meaningful conclusions. Although Epidiolex® is safe for human consumption, recent changes in regulation of commercially available CBD products have resulted in limited quality control and products marketed with unknown CBD bioavailability. Even scientifically rigorous studies have used different sources of CBD and different suspension vehicles for administration, making it difficult to compare results among studies and resolve mixed outcomes.. This paper reviews the molecular targets, pharmacokinetics, and safety and abuse liability of CBD; additionally, the extant evidence on its potential therapeutic effects for neurological disorders, pain, inflammation, conditions related to immune function, psychiatric disorders, and substance use are described.

Topics: Cannabidiol; Child; Humans; Mental Disorders; Nervous System Diseases; Pain; Substance-Related Disorders; United States; United States Food and Drug Administration

Substance use disorder (SUD) is a serious public health problem worldwide for which available treatments show limited effectiveness. Since the legalization of cannabis and the approval of cannabidiol (CBD) by the US Food and Drug Administration, therapeutic potential of CBD for the treatment of SUDs and other diseases has been widely explored. In this mini-review article, we first review the history and evidence supporting CBD as a potential pharmacotherapeutic. We then focus on recent progress in preclinical research regarding the pharmacological efficacy of CBD and the underlying receptor mechanisms on addictive-like behavior. Growing evidence indicates that CBD has therapeutic potential in reducing drug reward, as assessed in intravenous drug self-administration, conditioned place preference and intracranial brain-stimulation reward paradigms. In addition, CBD is effective in reducing relapse in experimental animals. Both in vivo and in vitro receptor mechanism studies indicate that CBD may act as a negative allosteric modulator of type 1 cannabinoid (CB1) receptor and an agonist of type 2 cannabinoid (CB2), transient receptor potential vanilloid 1 (TRPV1), and serotonin 5-HT

Topics: Animals; Behavior, Animal; Brain; Cannabidiol; Cannabinoids; Disease Models, Animal; Dopamine; Humans; Methamphetamine; Piperidines; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptor, Serotonin, 5-HT1A; Recurrence; Reward; Self Administration; Substance-Related Disorders; TRPV Cation Channels

Cannabis is the most widely used illicit drug. The two most important natural cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The THC content of cannabis has been increasing during the last years and recently appeared in the market as a series of synthetic cannabinoids with potent agonist activity. Recreational users frequently combine cannabis with other drugs of abuse as alcohol, amphetamines and derivatives, nicotine and cocaine. In addition, these subjects can be taking medicines for acute and chronic medical conditions. The increasing use of medicinal cannabis for chronic pain and neurological and psychiatric disorders can produce potential interactions with medications used for the symptomatic treatment of these or other diseases.. THC and CBD are metabolized mainly in the liver by cytochrome P-450 isoenzymes (mainly CYP2Cs and CYP3A4). In vitro studies indicate that THC and CBD both inhibit CYP1A1, 1A2 and 1B1 enzymes, and recent studies have indicated that CBD is also a potent inhibitor of CYP2C19 and CYP3A4. Both cannabinoids may interact with other medications metabolized by the same pathway or by inducers/inhibitors of the isoenzymes. Cannabis produces sedation, impairs psychomotor performance, and increases blood pressure and heart rate. Pharmacodynamic interactions with other sedatives can potentiate the central effects but can be decreased by psychostimulants. This review focuses on the interactions between cannabinoids and alcohol, other drugs of abuse, and prescription medicines.

Topics: Cannabidiol; Dronabinol; Drug Interactions; Humans; Illicit Drugs; Psychotropic Drugs; Substance-Related Disorders

Topics: Animals; Anti-Anxiety Agents; Anxiety Disorders; Brain; Cannabidiol; Emotions; Fear; Humans; Learning; Substance-Related Disorders

Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ(9)-tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from "medical CBD" and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant.

Topics: Analgesics, Opioid; Animals; Cannabidiol; Humans; Recurrence; Substance-Related Disorders

There is a growing consensus that cannabis dependence is a substantial and underappreciated problem. The key component responsible for the euphoric effects of cannabis and its dependence potential is δ-9-tetrahydrocannabinol (THC). THC-containing cannabinoid medicines theoretically pose a risk of abuse and dependence.. In order to evaluate the potential of Sativex to cause cannabis-like psychoactivity, abuse or dependence relevant data from all published papers have been reviewed along with the integrated safety analysis for Sativex use in multiple sclerosis (MS) patients on file at GW Pharmaceuticals.. In clinical trials, intoxication scores have been low and euphoria reported by only 2.2% of patients. Tolerance has not occurred, abrupt withdrawal has not resulted in a formal withdrawal syndrome, and no cases of abuse or diversion have been reported to date. A formal abuse liability study of Sativex in experienced cannabis smokers showed some abuse potential in comparison with placebo at higher doses, but scores were consistently lower than equivalent doses of THC. Evidence to date suggests that abuse or dependence on Sativex is likely to occur in only a very small proportion of recipients.

Topics: Cannabidiol; Cannabinoids; Clinical Trials as Topic; Dronabinol; Drug Combinations; Humans; Marijuana Abuse; Multiple Sclerosis; Plant Extracts; Psychotropic Drugs; Randomized Controlled Trials as Topic; Substance-Related Disorders

Chronic cannabis use is associated with impaired cognitive function. Evidence indicates cannabidiol (CBD) might be beneficial for treating cannabis use disorder. CBD may also have pro-cognitive effects; however, its effect on cognition in people with cannabis use disorder is currently unclear.. We aimed to assess whether a 4-week CBD treatment impacted cognitive function. We hypothesised that CBD treatment would improve cognition from baseline to week 4, compared to placebo.. Cognition was assessed as a secondary outcome in a phase 2a randomised, double-blind, parallel-group and placebo-controlled clinical trial of 4-week daily 200 mg, 400 mg and 800 mg CBD for the treatment of cannabis use disorder. Participants had moderate or severe DSM-5 cannabis use disorder and intended to quit cannabis use. Our pre-registered primary cognitive outcome was delayed prose recall. Secondary cognitive outcomes were immediate prose recall, stop signal reaction time, trail-making task performance, verbal fluency and digit span.. Seventy participants were randomly assigned to placebo (n = 23), 400 mg CBD (n = 24) and 800 mg CBD (n = 23). A 200 mg group was eliminated from the trial because it was an inefficacious dose at interim analysis (n = 12) and was not analysed here. For the primary cognitive outcome, there was no effect of CBD compared to placebo, evidenced by a lack of dose-by-time interaction at 400 mg (0.46, 95%CIs: - 1.41, 2.54) and 800 mg (0.89, 95%CIs: - 0.99, 2.81). There was no effect of CBD compared to placebo on secondary cognitive outcomes, except backwards digit span which increased following 800 mg CBD (0.30, 95%CIs: 0.02, 0.58).. In this clinical trial for cannabis use disorder, CBD did not influence delayed verbal memory. CBD did not have broad cognitive effects but 800 mg daily treatment may improve working memory manipulation.. The trial was registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013-000,361-36).

Topics: Cannabidiol; Cannabis; Cognition; Double-Blind Method; Hallucinogens; Humans; Marijuana Abuse; Substance-Related Disorders

Cocaine use disorder (CUD) is associated with various cognitive deficits that impede patients' functionality, prognosis and therapeutic outcomes. New pharmacological treatments for CUD that could improve cognition are needed.. To explore whether cannabidiol (CBD) is superior to placebo to improve cognitive functioning in individuals with CUD.. We conducted an exploratory analysis of a single site, randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy in reducing craving, cocaine use and relapse in individuals with CUD. Seventy-eight individuals diagnosed with CUD were randomized to receive either CBD (800 mg) or placebo for 92 days. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess inhibition (Stop Signal Task; SST), risky decision making (Cambridge Gambling Task; CGT) and visual memory (Pattern Recognition Memory; PRM). This assessment was made on day 1, day 7 and at week 6. We controlled for sex, severity of dependence and baseline cognitive scores in our generalized estimating equation models.. Both groups performed similarly on the PRM (correct answers: p = 0.080), SST (stop signal reaction time: p = 0.644) and CGT (quality of decision making: p = 0.994; deliberation time: p = 0.507; delay aversion: p = 0.968; risk taking: p = 0.914) tests.. We found no evidence for 800 mg of CBD to be more efficacious than placebo for improving cognitive outcomes. Clinical trials evaluating pharmacological treatments for CUD should continue to be a research priority.

Topics: Cannabidiol; Cocaine; Cocaine-Related Disorders; Cognition; Craving; Double-Blind Method; Humans; Substance-Related Disorders

There is increasing interest and evidence for the use of cannabinoid medications in the treatment of cannabis use disorder, but little examination of the correlates of successful treatment. This paper is a secondary analysis of a randomised placebo-controlled trial of nabiximols for the treatment of cannabis use disorder (CUD), aiming to identify which client and treatment characteristics impact treatment engagement and outcomes.. Bayesian multiple regression models were used to examine the impact of age, gender, duration of regular cannabis use, daily quantity of cannabis, cannabis use problems, self-efficacy for quitting, sleep, mental health, pain measures, and treatment group upon treatment engagement (retention, medication dose, and counselling participation) and treatment outcomes (achieving end-of-study abstinence, and a 50% or greater reduction in cannabis use days) among the 128 clients participating in the 12-week trial.. Among the treatment factors, greater counselling attendance was associated with greater odds of abstinence and ≥ 50% reduction in cannabis use; nabiximols with greater odds of ≥ 50% reduction and attending counselling, and reduced hazard of treatment dropout; and higher dose with lower odds of ≥ 50% reduction. Among the client factors, longer duration of regular use was associated with higher odds of abstinence and 50% reduction, and lower hazard of treatment dropout; greater quantity of cannabis use with reduced hazard of dropout, greater odds of attending counselling, and higher average dose; greater pain at baseline with greater odds of ≥ 50% reduction and higher average dose; and more severe sleep issues with lower odds of ≥ 50% reduction. Males had lower odds of attending counselling.. These findings suggest that counselling combined with agonist pharmacotherapy may provide the optimal treatment for cannabis use disorder. Younger clients, male clients, and clients with sleep issues could benefit from extra support from treatment services to improve engagement and outcomes.. Australian New Zealand Clinical Trials Registry (ACTRN12616000103460) https://www.anzctr.org.au.

Topics: Australia; Bayes Theorem; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Humans; Male; Marijuana Abuse; Pain; Substance-Related Disorders

Cocaine use disorder (CUD) is a major public health issue associated with physical, social, and psychological problems. Excessive and repeated cocaine use induces oxidative stress leading to a systemic inflammatory response. Cannabidiol (CBD) has gained substantial interest for its anti-inflammatory properties, safety, and tolerability profile. However, CBD anti-inflammatory properties have yet to be confirmed in humans. This exploratory study is based on a single-site randomized controlled trial that enrolled participants with CUD between 18 and 65 years, randomized (1:1) to daily receive either CBD (800 mg) or placebo for 92 days. The trial was divided into a 10-day detoxification (phase I) followed by a 12-week outpatient follow-up (phase II). Blood samples were collected from 48 participants at baseline, day 8, week 4, and week 12 and were analyzed to determine monocytes and lymphocytes phenotypes, and concentrations of various inflammatory markers such as cytokines. We used generalized estimating equations to detect group differences. Participants treated with CBD had lower levels of interleukin-6 (p = 0.017), vascular endothelial growth factor (p = 0.032), intermediate monocytes CD14

Topics: Cannabidiol; Cocaine; Double-Blind Method; Humans; Substance-Related Disorders; Vascular Endothelial Growth Factor A

Previous studies suggest cannabinoid agonist treatment is effective in reducing cannabis use in dependent treatment seekers, however few studies have reported on post-treatment outcomes. We examine cannabis use outcomes 12 weeks after cessation of treatment from a randomised placebo-controlled trial of nabiximols for the treatment of cannabis dependence.. 128 participants received either nabiximols (n = 61) or placebo (n = 67) for 12 weeks, in combination with psychosocial interventions. Self-reported number of days of cannabis use in the previous 28 days was measured at baseline, 4, 8, and 12 weeks (end of treatment) and again at 24 weeks (3 months after treatment ceased). Urinalysis was used to confirm self-report data at Week 24 interview.. A factorial mixed-effects model for repeated measures regression revealed that the nabiximols group used cannabis on 6.8 fewer days in the previous 28 days at week 12 (end of treatment) than the placebo group (p = 0.002, CI: 2.1,11.4), and 6.7 fewer days in the previous 28 days at the week-24 follow-up than the placebo group (p = 0.006, CI: 1.4,12.1). A significantly higher proportion of the nabiximols group (14/61; 23 %) than the placebo group (6/67; 9%) reported abstinence from cannabis in the previous 28 days at the week-24 research interview OR=3.0, CI: 1.1, 9.1; p=0.035, NNT=8, CI: 4, 71).. The benefits of treatment incorporating nabiximols with psychosocial interventions in reducing cannabis use appears to persist for up to 3 months after the cessation of treatment. A stepped care model of treatment is proposed.. Australian New Zealand Clinical Trials Registry (ACTRN12616000103460) https://www.anzctr.org.au.

Topics: Australia; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Dronabinol; Drug Combinations; Female; Humans; Male; Marijuana Abuse; Marijuana Smoking; Substance-Related Disorders; Treatment Outcome

Treatment with a highly purified oral solution of cannabidiol (CBD), derived from the plant Cannabis sativa L., demonstrated some evidence of central nervous system (CNS)-related adverse events in patients enrolled in phase 3 trials for treatment of childhood-onset epilepsy. Cannabidiol was categorized as a Schedule 1 substance by the United States Drug Enforcement Administration; therefore, it was important to test CBD for human abuse potential.. This was a single-dose, randomized, double-blind, double-dummy, placebo- and active-controlled crossover trial. The abuse potential of single oral doses of plant-derived pharmaceutical formulations of highly purified CBD (Epidiolex®; 750 mg, 1500 mg, and 4500 mg) was compared with that of single oral doses of alprazolam (2 mg), dronabinol (10 mg and 30 mg), and placebo in healthy recreational polydrug users. The primary endpoint to assess abuse potential was the maximum effect (E. Administration of a therapeutic dose of CBD (750 mg) showed significantly low abuse potential in a highly sensitive population of polydrug users. Although high and supratherapeutic doses of CBD (1500 mg and 4500 mg, respectively) had detectable subjective effects compared with placebo; the effects were significantly lower than those observed with alprazolam and dronabinol.

Topics: Adolescent; Adult; Cannabidiol; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Illicit Drugs; Male; Middle Aged; Risk Assessment; Substance-Related Disorders; Young Adult

There is currently no pharmacological treatment approved for cannabis dependence. In this proof of concept study, we assessed the feasibility/effects of fixed and self-titrated dosages of Sativex (1:1, Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD)) on craving and withdrawal from cannabis among nine community-recruited cannabis-dependent subjects.. Participants underwent an 8-week double-blind placebo-controlled trial (an ABACADAE design), with four smoke as usual conditions (SAU) (A) separated by four cannabis abstinence conditions (B-E), with administration of either self-titrated/fixed doses of placebo or Sativex (up to 108 mg THC/100 mg CBD). The order of medication administration during abstinence conditions was randomized and counterbalanced. Withdrawal symptoms and craving were assessed using the Cannabis Withdrawal Scale (CWS), Marijuana Withdrawal Checklist (MWC) and Marijuana Craving Questionnaire (MCQ). Medication use was assessed during the study by means of self-reports, vial weight control, toxicology and metabolite analysis. Cannabis use was assessed by means of self-reports.. High fixed doses of Sativex were well tolerated and significantly reduced cannabis withdrawal during abstinence, but not craving, as compared to placebo. Self-titrated doses were lower and showed limited efficacy as compared to high fixed doses. Participants reported a significantly lower "high" following Sativex or placebo as compared to SAU conditions. Cannabis/medication use along the study, as per self-reports, suggests compliance with the study conditions.. The results found in this proof of concept study warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence.

Topics: Adult; Cannabidiol; Cannabis; Craving; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Marijuana Abuse; Marijuana Smoking; Middle Aged; Plant Extracts; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome; Young Adult

Topics: Animals; Behavior, Addictive; Cannabidiol; Cannabis; Rats; Substance-Related Disorders

Cannabis is the main illicit psychoactive substance used by pregnant women in France. The aim of the present national survey was to describe adverse events (AEs) of recreational cannabis use during pregnancy reported to the French Addictovigilance Network (FAN). Spontaneous reports (SRs) of AEs related to recreational cannabis use during pregnancy were collected by the FAN between 01/01/2011 and 31/01/2021 (excluding cannabidiol and synthetic cannabinoids). Over the study period, 160 SRs involved cannabis use alone or in association with tobacco (59% of all SRs) which increased. Among the 175 maternal AEs, the most commons were psychiatric AEs experienced by 96 (64.9%) women, in particular cannabis use disorders (n = 89, 60.1%), dependence (n = 54, 36.5%) and abuse (n = 21, 14.2%). Among the 57 fetal AEs, the most common were heart rhythm disorders that affected 25 (16.9%) fetuses and intrauterine growth restriction (IUGR) (n = 20, 13.5%). Among the 140 neonatal AEs, the most common were IUGR experienced by 39 (26.3%) newborns and prematurity (n = 32, 21.6%). Twelve cases of congenital malformations were observed and 4 intrauterine/neonatal deaths. Furthermore, some of these AEs (n = 13) were unexpected. Cannabis use during pregnancy has problematic consequences for both mothers and infants who need close monitoring.

Topics: Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Female; Fetal Growth Retardation; Hallucinogens; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Male; Pregnancy; Substance-Related Disorders

In this report, we present a case of a 16,9-year-old patient with multiple substance use disorder (cannabis, MDMA, cocaine, ecstacy), severe depression, social phobia and narcissistic personality disorder.We administered Cannabidiol (CBD) capsules in different dosages (starting dosage 100 mg up to 600 mg over 8 weeks) after unsuccessful treatment with antidepressants.CBD was a safe and well tolerated medication for this patient. Upon treatment with CBD and cessation of the antidepressant medication, the patient improved regarding depressive as well as anxiety symptoms including simple phobias and symptoms of paranoia and dissociation. Furthermore, the patient quit abusing illegal drugs including THC without showing withdrawal symptoms. This is the first report of CBD medication in a patient with multiple substance use disorder with a positive outcome.Until today it is not clear if CBD holds promise as a therapeutic option in substance use disorder as RCTs are lacking, but in this single case the substance seems to work in various domains.. Wir präsentieren den Fall eines 16,9 Jahre alten Patienten, der aufgrund eines multiplen Substanzmissbrauches (Cannabis, MDMA, Kokain, Ecstacy), schwerer depressiver Symptomatik, einer Sozialphobie und einer narzisstischen Persönlichkeitsstörung behandelt wurde.Wir verschrieben Cannabidiol (CBD) in Kapselform in unterschiedlichen Dosierungen (100 mg bis 600 mg pro Tag über 8 Wochen), nachdem die antidepressive Medikation keine Symptomreduktion brachte.CBD wurde zu allen Zeiten gut vertragen. Auch nach Beendigung der antidepressiven Medikation profitierte der Patient bezüglich der depressiven Symptomatik, der Angstsymptomatik sowie paranoider und dissoziativer Symptomatik. Außerdem konsumierte der Patient während der Behandlung keine weiteren Substanzen wie THC oder andere illegalen Drogen, ohne dass es zum Auftreten von Entzugserscheinungen kam.Es ist noch nicht erwiesen, ob CBD eine alternative Therapieoption bei Patienten mit multiplem Substanzabusus darstellt, da keine randomisiert-kontrollierten Studien publiziert sind. Bei unserer Fallstudie konnten wir eine Wirksamkeit in verschiedenen Bereichen der Psychopathologie beobachten.

Topics: Adolescent; Anxiety; Cannabidiol; Cannabis; Child; Depression; Humans; Substance-Related Disorders

Cannabidiol (CBD) is gaining considerable attention in the research community with promising results in a variety of neuropsychiatric conditions. In particular, there are replicated findings for the therapeutic effects of CBD on psychotic and anxiety symptoms as well as substance use disorders, all of which are highly prevalent in patients who present with suicidality. Meanwhile, there has been a lack of suicide research on cannabidiol. This perspective provides an overview of the available evidence, potential reasons behind the halt in suicide research on cannabidiol, and recommendations for future investigations.

Topics: Anxiety; Cannabidiol; Humans; Substance-Related Disorders; Suicide

Methylphenidate (MPH) is a mild CNS stimulant that has been used in hyperactive children, and patients with neurodegenerative and major depressive disorders. Exposure to MPH-associated cues enhances craving and arousal in drug users. On the other hand, cannabidiol (CBD) has antipsychotic potential that might be useful in alleviating symptoms of drug addiction. The aim of this study was to investigate the effect of CBD administration on extinction and reinstatement of MPH-induced conditioning place preference (CPP) in rats. Male rats received MPH (1, 2.5 or 5 mg/kg, i.p) or morphine (5 or 10 mg/kg, s.c.) during the conditioning phase. Following the establishment of CPP, during extinction training, 60 min prior to every CPP session, animals were given daily ICV CBD (10 or 50 μg/5 μL), vehicle alone (DMSO) 10 % or were treatment-naïve. On the reinstatement day animals after receiving the initial dose of MPH, 0.5 mg/kg, and were placed into the CPP box to evaluate the CPP scoring for 10-min. Our findings indicated that morphine (5 and 10 mg/kg; s.c.) and MPH (1 and 2.5 mg/kg; i.p.) induced a CPP. The ICV administration of both doses of CBD (10 and 50 μg/5 μL) prevented the reinstatement of MPH-induced CPP, which displayed shorter extinction latency compared to treatment-naïve or DMSO 10 % groups. Therefore, CBD's site of action is a potential target for reducing the risk of MPH relapse; however, more investigation is required.

Topics: Animals; Cannabidiol; Central Nervous System Stimulants; Conditioning, Psychological; Extinction, Psychological; Male; Methylphenidate; Rats; Rats, Wistar; Substance-Related Disorders

Cannabidiol (CBD) is purportedly a promising therapeutic agent to provide relief for a variety of medical conditions with mild or no psychoactive effects. However, little is known about young adults who use cannabis and CBD-dominant products, and associations between CBD use and other drug use.. Young adults (aged 24-32) who currently used cannabis (n = 239) were surveyed in Los Angeles in March 2019 through March 2020. The sample was divided into CBD-dominant (at least 1:1 CBD:THC ratio) and THC-dominant product users. We described CBD forms, reasons and conditions for CBD use and examined between-group differences in sociodemographic characteristics, cannabis practices, health and other drug use.. CBD-dominant users were more likely to be female, use cannabis at lower frequency and amount (except for edible/drinkable/oral products), self-report medical motivation for cannabis use, use cannabis for pain and report more health problems. Oil, flower, topicals and sprays/drops/tinctures were the most prevalent CBD forms. Psychological problems and pain were commonly reported conditions and medical reasons for CBD use. CBD-dominant users were more likely to report illicit drug use, where psilocybin use was markedly different between the two groups.. CBD use was associated with health histories and motivations linked to pain and psychological problems. Positive association between CBD use and illicit drug use may indicate self-medication for psychological conditions. Future studies should evaluate the effectiveness of various CBD forms and dose regimens for treatment of pain and psychological problems, and as a potential intervention for decreasing other drug use and associated harms.

Topics: Adolescent; Adult; Cannabidiol; Cannabis; Cohort Studies; Dronabinol; Female; Hallucinogens; Humans; Longitudinal Studies; Los Angeles; Male; Marijuana Use; Pain; Self Report; Substance-Related Disorders; Young Adult

Topics: Cannabidiol; Humans; Secondary Prevention; Substance-Related Disorders

To estimate prevalence of continuous use (persistence) of prescribed cannabinoid medications for up to 1 year from initial prescription in Manitoba, Canada and predictors of duration of use.. A retrospective, population-based, cohort study using administrative data from the Manitoba Population Research Data Repository located at the Manitoba Centre for Health Policy, Canada.. People without a record of a previous prescription who were prescribed a cannabinoid medication from 1 April 2004 to 1 April 2016 followed for 1 year from the date of first prescription.. Continuous prescribed cannabinoid medication use was defined as use without a gap exceeding 60 days between prescriptions. The primary outcome was prevalence of continuous prescribed cannabinoid medication use for up to 1 year. A secondary outcome was duration of continuous use. Predictors were socio-demographic characteristics, medical diagnoses and type of cannabinoid medication.. Among 5452 new users, 18.1% [95% confidence interval (CI) = 17.08-19.12] were still using cannabinoids at 1 year. Median duration of use was 31 days [interquartile range (IQR) = 25-193]. This was highest for nabilone (33 days, IQR = 25-199) and lowest for nabiximols (20 days, IQR = 7-30). Use was longest among 19-45- and 46-64-year-old users and those with the highest socio-economic status. Fibromyalgia [hazard ratio (HR) = 0.89, 95% CI = 0.84-0.95], osteoarthritis (HR = 0.91, 95% CI = 0.82-0.97) and substance use disorder (HR = 0.85, 95% CI = 0.76-0.94) diagnoses were associated with longer use (HR for discontinuation-HR < 1 less discontinuation and longer use). A diagnosis of cancer was associated with shorter use (HR = 2.73, 95% CI = 2.02-3.67).. In Manitoba, Canada approximately 18% of people prescribed cannabinoid medication continue using for at least 1 year. Duration of use varies with type of cannabinoid medication, age, socio-economic status and dagnosis.

Topics: Adolescent; Adult; Aged; Cannabidiol; Cannabinoids; Dronabinol; Drug Combinations; Duration of Therapy; Female; Fibromyalgia; Humans; Male; Manitoba; Medication Adherence; Middle Aged; Neoplasms; Osteoarthritis; Prescription Drugs; Retrospective Studies; Social Class; Substance-Related Disorders; Young Adult

Most countries have laws against driving while impaired by drugs. However, in many countries, including Canada and the United States, police must have individualized suspicion that the driver has recently used an impairing substance before they can gather the evidence required for laying a criminal charge. This report studies police documentation of drug involvement among drivers who had a motor-vehicle crash after using an impairing substance.. We obtained blood samples and police reports on injured drivers treated in participating British Columbia trauma centres following a crash. Blood was analyzed for alcohol, cannabinoids, other recreational drugs, and impairing medications. Corresponding police reports were examined to determine whether police recorded that the driver's ability was impaired by alcohol, drug or medication, or that one of these substances was a possible contributory factor in the crash.. We obtained blood samples and corresponding police reports on 1816 injured drivers. Mean driver age was 44 years, 63.2% were male, and 25.8% were admitted to hospital. Alcohol was detected in 272 drivers (15.0%), THC (tetrahydrocannabinol - the principal psychoactive ingredient in cannabis) in 136 (7.5%), other recreational drugs in 166 (9.1%), and potentially impairing medications in 363 (20.0%). Police reported that the driver's ability was impaired by alcohol or that alcohol was a possible contributory factor in 64.1% of the crashes involving alcohol-positive drivers. Drug impairment or drugs as a possible contributory factor was reported in 5.9% of the crashes involving THC-positive drivers, and in 16.9% of the crashes involving drivers who tested positive for other recreational drugs. Medication impairment was reported in only 2.2% of the crashes involving medication-positive drivers.. Police seldom document drug involvement in drivers who were in a crash after using cannabis, other recreational drugs or potentially impairing medications. This finding raises serious concerns about the ability of the police to effectively enforce current drug-impaired driving laws and public health officials' continued reliance on police crash reports to monitor the prevalence of drug-impaired driving.

Topics: Accidents, Traffic; Adult; Aged; Alcohol Drinking; Automobile Driving; British Columbia; Cannabidiol; Cannabis; Documentation; Driving Under the Influence; Dronabinol; Drug Combinations; Ethanol; Female; Humans; Illicit Drugs; Law Enforcement; Male; Middle Aged; Police; Prevalence; Substance-Related Disorders; Trauma Centers; United States; Young Adult

Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders. Recently, CBD has also been explored for potential in treating drug addiction. Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control. Here, we evaluated the "anti-relapse" potential of a transdermal CBD preparation in animal models of drug seeking, anxiety and impulsivity. Rats with alcohol or cocaine self-administration histories received transdermal CBD at 24 h intervals for 7 days and were tested for context and stress-induced reinstatement, as well as experimental anxiety on the elevated plus maze. Effects on impulsive behavior were established using a delay-discounting task following recovery from a 7-day dependence-inducing alcohol intoxication regimen. CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. Following treatment termination, reinstatement remained attenuated up to ≈5 months although plasma and brain CBD levels remained detectable only for 3 days. CBD also reduced experimental anxiety and prevented the development of high impulsivity in rats with an alcohol dependence history. The results provide proof of principle supporting potential of CBD in relapse prevention along two dimensions: beneficial actions across several vulnerability states and long-lasting effects with only brief treatment. The findings also inform the ongoing medical marijuana debate concerning medical benefits of non-psychoactive cannabinoids and their promise for development and use as therapeutics.

Topics: Administration, Cutaneous; Alcoholism; Animals; Anxiety; Brain; Cannabidiol; Cocaine-Related Disorders; Drug-Seeking Behavior; Impulsive Behavior; Male; Motor Activity; Rats; Rats, Wistar; Recurrence; Stress, Psychological; Substance-Related Disorders

Topics: Cannabidiol; Cannabinol; Cocaine; Dronabinol; Gas Chromatography-Mass Spectrometry; Humans; Limit of Detection; Opiate Alkaloids; Substance Abuse Detection; Substance-Related Disorders; Tooth

The objective of this investigation was to study the influence of the dose ratio between cannabidiol (CBD) and delta 9-tetrahydrocannabinol (delta 9-THC) on the effects of mixtures of the two cannabinoids on variable-interval (VI) schedule performance in rats. The effect on VI performance of a control solution, 10 mg/kg CBD, delta 9-THC (0.125, 0.5, 2 and 8 mg/kg) and a mixture of 10 mg/kg CBD + delta 9-THC (0.125, 0.5, 2 and 8 mg/kg) was investigated in 10 rats, with a different sequence of treatments for each animal. The results were expressed in terms of rate-dependency. The control solution, 10 mg/kg CBD, 0.125 mg/kg delta 9-THC, or 10 mg/kg CBD + delta 9-THC (0.125 mg/kg) did not cause rate-dependent effects. Delta 9-THC (0.5 and 2 mg/kg) produced rate-dependent effects. The dose of 8 mg/kg delta 9-THC almost suppressed responding. The combination of 10 mg/kg CBD + 0.5 mg/kg delta 9-THC did not cause rate-dependent effects but produced a response pattern similar to that obtained with 0.125 mg/kg delta 9-THC. At these doses CBD antagonized delta 9-THC. The combination of 10 mg/kg CBD + 2 mg/kg delta 9-THC caused rate-dependent effects. The rate-dependent regression line determined by this mixture was parallel to that produced by 2 mg/kg delta 9-THC. However, the lower intercept of the mixture with the y axis suggested potentiation of the depressant effects of delta 9-THC by CBD.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cannabidiol; Cannabinoids; Conditioning, Operant; Dose-Response Relationship, Drug; Dronabinol; Drug Combinations; Humans; Male; Rats; Rats, Inbred Strains; Substance-Related Disorders

Three basic procedures from the "underground press" for increasing the potency of marijuana were tested quantitatively: Black Merta, Dry Ice, and isopropanol--water extraction. In all methods there was not significant change in THC, CBN, or CBD content before and after treatment. The persistence of procedures which have no measurable effect on the chemical properties of the drug is presented as additional evidence for the importance of psychological factors in perceived drug effects.

Topics: Cannabidiol; Cannabinol; Cannabis; Cognitive Dissonance; Dronabinol; Humans; Spectrophotometry; Substance-Related Disorders